Congenital malformations& dysmorphic syndromes Flashcards Preview

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Flashcards in Congenital malformations& dysmorphic syndromes Deck (20)
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How can we classify malformation

-Major: causes significant medical or cosmetic problems( spina bifida) or cleft palette
-Minor: Of no medical significance e.g accessory nipple, single palmar crease
-Single malformation: often multifactorial
-Multiple: often genetic


What is amniotic band syndrome?

-Occurs when the unborn baby (fetus) becomes entangled in fibrous string-like amniotic bands in the womb, restricting blood flow and affecting the baby's development
-If a band wraps tightly around a limb, the limb can actually be completely amputated. If the band is across the baby's face it can cause cleft palate.


Outline chromosome rearrangements

1.) Number
-Aneuploidies ( chrom number not divisible by the haploid number)
-Polyploidies (multiple sets of chromosome)
2.) Structure
-Balanced translocations
-Unbalanced: deletions;duplications;inversions;translocations

Often associated with problems


Outline trisomy 21

-Intellectual disability: mild to moderate learning difficulties
-Cardiac defects eg AVSD can be primary trisomy 21 or a translocation 46,Xn, der(14;21) (q10;q10) +21


Outline trisomy 18

-Edward syndrome
-Severe mental disability
-Dysmorphic: micrognathia; prominent occiput; clenched overlapping fingers; prominent heels& rocker-bottom feet; cardiac defects
-Primary trisomy 18 47,XX +18 or 47 XY +18


Outline trisomy 13

-Patau syndrome
-Severe mental disability
-Dysmorphic: cleft lip, cleft palate; holoprecencephaly; postaxial polydactyly; renal abnormalities; cardiac defects
-45% die within 1 months, 85% withing 1 year
-primary trisomy 47,XX+13
-Unbalanced translocation 46, Xn, +13, der(13,14)(q10;q10)


Outline del22q11.2

-deletion of a section of chromosome 22
-CATCH 22/DiGeorge syndrome/ velocardiofacial syndrome
-CHD (conotruncal anomaly)
-Cleft lip and/or palate
-Absent thymus
-Absent parathyroid glands
-Dysmorphic features
-Learning difficulties


What is williams syndrome

-developmental delay
-very happy & sociable
-May have congenital heart problems


Outline the features of del16p11.2

-Learning difficulties
-schizophrenia, bipolar,depression
-Obesity in young adults
-Also unaffected individuals
-525kb deletion, containing 25 genes


Using the example of Noonan syndrome, explain how mutations in genes which function within the same pathway may cause similar but distinct clinical phenotypes

-Noonan syndrome is caused by changes in one of several autosomal dominant genes.
-Noonan syndrome is a disorder that involves unusual facial characteristics, short stature, heart defects present at birth, bleeding problems, developmental delays, and malformations of the bones of the rib cage.
Some phenotypic overlap with:
-Neurofibromatosis type 1: especially NF1 & valvular pulmonary stenosis( similar Noonan like facies- aka Watson syndrome)
-Cardio-facial-cutaneous syndrome: more severe learning difficulties & sparse hair/lack of eyebrows
-Costello syndrome: severe developmental delay & learning difficulties& increased risk of malignancy


What factors affect gene expression and penetrance

-Modifier genes
-Hormonal/reproductive factors
-Response to DNA damage


Outline Duchenne muscular dystrophy

-onset age 3-6yrs
-Progressive weakness
-Pseudohypertrophy of calf muscles
-Spinal deformity
-Cardiopulmonary involvement
-Mild-moderate mental retardation
-X-linked recessive


How does alphafetoprotein reach maternal serum

AFP reaches maternal serum:
-directly across placenta
-Indirectly from amniotic fluid across chorion & amnion
-and uptake by maternal vasculature in uterine decidua
-Levels change with gestation (lower in 2nd than 1st trimester)
-used in the quadruple test to screen for NTDs and downsyndrome


What does the quadriple test involve

screening 0involving
-Alpha-feto protein (high levels=bad)
- unconjugated estriol (low=bad)
-human chorionic gonadotrophin (VERYhigh= bad)
-inhibin A (high= bad)


What is the significance of PAPP-A

-used for screening; 12 week combined screening test
-low levels can be associated with downsyndrome
-Levels less than 0.5 =low
- hormone that is produced by the placenta in pregnancy


What are indirect cranial/cerebellar markers?

1.) lemon sign:
-a feature when there appears to be an indentation of the frontal bone (depicting that of a lemon)
-seen in most fetuses with spina bifida
2.) Banana sign:
-abnormal curvature of the cerebellum noted on ultrasound imaging in a fetus
-Absent cisterna magna


What is ventriculomegaly

-aka hydrocephalus, is a condition in which the CSF-filled structures within the brain become larger than normal.
-The large ventricles can inhibit the proper development of the brain.


What other invasive techniques are used in prenatal diagnosis?

-Fetal skin biopsy: for hereditary skin disorders eg epidermolysis bullosa
-Fetal blood sampling (cordocentesis): chromosomal disorders; haematological disorders; congenital infection


Outline myotonic dystrophy

-Autosomal dominant
-Distal myopathy
-Prolonged muscle contraction
-Heart conduction defect
-diabetes mellitus
-early onset cataract
-triplet repeat disorder


Outline congenital myotonic dystrophy

-Genomic anticipation
-most severe form
-congenital hypotonia
-joint contractures (talipes)
-respiratory failure
-facial weakness
-swallowing difficulties
-developmental delay
-autism spectrum disorder
-triplet repeat disorder